PRESENTATION ABSTRACTS
(BayesR) and a cross-population extended haplotype test (XP-EHH) to search for disease-asso- ciated selective sweeps in four dog breeds at risk for AD. We discovered 15 associated loci and eight candidate regions under selection. Eleven associated loci explained ~33% of AD variance in Labrador retrievers (LR). Effect variants on chr17 were syntenic to the major genetic risk locus in human AD. Selection signals were detected across the TBC1D1 gene (body weight) in AD cases of show type LR and the LRP1B gene (cognition), close to the KYNU gene (psoriasis), in working type German shepherd controls. STRING enrichment analysis highlighted the integrin alpha (ITGA) pathway represented by four ITGA genes from different BayesR loci in LR and golden retrievers. Other significant enrichment terms with multiple loci represented were related to Leukemia, connective tissue, and MyD88-dependent toll-like receptor. Candidate genes from AD-associated BayesR and selection regions were assigned to functions in the epidermis and/or immunity. In con- clusion, we identified candidate genes and pathways with potential relevance to the pathogenesis of canine AD. #29 Recently derived, full-length gene retrocopies occur frequently in dogs Kevin Batcher 1 , Scarlett Varney 1 , Daniel York 2 , Verena Affolter 3 , Steven G. Friedenberg 4 , Matthew Blacksmith 5 , Jeffrey M. Kidd 5,6 , Robert Rebhun 2 , Peter Dickinson 2 , and Danika Bannasch 1 klbatcher@ucdavis.edu 1 Department of Population Health and Reproduction, University of California, Davis, CA, USA, 2 Depart- ment of Surgical and Radiological Sciences, University of California, Davis, CA, USA, 3 Department of Pathology, Microbiology, & Immunology, University of California, Davis, CA, USA, 4 Department of Veter- inary Clinical Sciences, University of Minnesota, Saint Paul, MA, USA, 5 Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA, 6 Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA Gene retrocopies, which are formed through LINE1-mediated reverse transcription of mRNA, are often considered pseudogenes due to the accumulation of mutations and a presumed lack of function. However, most mammalian genomes contain active LINE1 which is capable of inserting new retrocopies called retrocopy number variants (retroCNVs). These retroCNVs are not typically identified from whole genome sequencing data using common variant calling techniques. While multiple recent, functional retroCNVs of the FGF4 gene have been identified in canids, the full landscape of retroCNVs has not been characterized. Here, a retroCNV discovery pipeline was developed and used on a whole-genome sequencing dataset consisting of 293 canids from 76 breeds. In total, 1,911 retroCNV insertion sites from 1,179 parent genes were identified in the dataset, 1,236 of which appeared identical to their parent gene sequence, highlighting their recent origin. Each dog had an average of 54.8 total retroCNVs and 1.4 private retroCNVs. Human genomes in comparison had an average of 4.2 retroCNVs per individual, highlighting a 13-fold relative increase in retroCNV frequency in dogs. Evidence for expression in testes was observed for 12% of the retroCNVs identified in 6 Golden Retrievers, including four chimeric transcripts, while in Poodle skin tissue, a retroCNV was identified disrupting the tissue specificity of a gene at the insertion site, resulting in a coat color phenotype. Additionally, 97 retroCNVs had significantly elevated FST across dog breeds, possibly indicating selection. RetroCNVs are an unexplored source of genetic variation in canids which play an important role in phenotypic diversity in dogs.
47
Made with FlippingBook - Online magazine maker